The term epilepsy is derived from a Greek word meaning a condition of being seized or overcome. The term epilepsy designates a group of central nervous system disorders having in common the occurrence of sudden and transitory episodes of abnormal behavioral symptoms of motor sensory, autonomic or psychic origin. Epilepsies have a definite onset and ending, and they usually are of short duration. Epilepsies are classified generally into two groups including generalized and partial, based on the type of seizures. Generalized seizures may involve a loss consciousness or convulsive movements, including tonic-clonic, myoclonic, tonic or clonic, and myoclonic astatic epilepsy. Partial seizures are divided into three subgroups including simple, complex, and secondarily generalized seizures.
Antiepileptic drugs are available for treating epilepsies. For example, valproic acid and its pharmaceutically acceptable salts are useful for treating epileptic phenomena. This drug is effective for its intended therapy; however, there are shortcomings associated with this drug. For instance, the antiepileptic drug valproic salt is extremely hygroscopic and liquifies very rapidly and it is sticky. The drug exhibits a short-half life that can lead to fluctuations in blood antiepileptic drug levels. These properties can interfere with the manufacture and release of the drug from a dosage form, and these shortcomings are serious drawbacks in the management of epilepsies.
Prior to this invention, the prior art administered an antiepileptic drug in a conventional dosage form like a tablet, or a capsule at repetitive dosing intervals. The prior art mode of therapy leads to a drug concentration in the blood during the dosing interval, and then a decrease in drug concentrations as a result of drug absorption, distribution, metabolism and elimination. The concentration difference in dosing intervals is related to the presence and to the absence of administered drug, which is a major disadvantage associated with conventional dosage forms. Conventional dosage forms and their mode of operation are discussed in Remington's Pharmaceutical Sciences, 18th Edition, pages 1676 to 1686 (1990), Mack Publishing Co.; The Pharmacological Basis of Therapeutics, 7th Edition, page 7, (1985) published by Macmillian Publishing Co.; Biopharmaceutics and Clinical Pharmacokinetics, 3rd Edition, pages 1 to 28, (1984), Published by Lea & Febiger, Philadelphia, Pa.; and in U.S. Pat. Nos. 3,598,122 and 3,598,123 both issued to Zaffaroni.
The above presentation concerns the critical need for a dosage form that overcomes the shortcomings of conventional dosage forms, including tablets, capsules, elixirs and suspensions. These conventional dosage forms produce the peaks and valleys patterns discussed above, and they do not provide for dosage-regulated drug therapy over an extended period of time. The drug is dosed by the prior art twice or trice a day, which does not lead to controlled and sustained therapy. This prior art pattern of drug administration speaks of the need for a dosage form that can administer the drug in a rate-controlled pattern over an extended time to provide constant therapy and thereby eliminate the need for multiple dosing of the drug.
The prior art provided controlled-release dosage forms that can administer a drug continuously over time for controlled-rate therapy, as in, for example, in U.S. Pat. No. 4,327,725 issued to Cortese and Theeuwes and in U.S. Pat. Nos. 4,612,008; 4,765,989; and 4,783,337 issued to Wong, Barclay, Deters, and Theeuwes. The dosage forms disclosed in these patents provided a controlled rate of drug delivery over an extended time to provide constant drug therapy and thereby eliminate the need for multiple dosing of the drug. These dosage forms can deliver many drugs for their therapy, but there are certain drugs that are not readily manufactured and delivered from dosage forms. For example, sodium valproate because of its hygroscopic and tacky nature does not lend itself for providing a dosage form for controlled extended delivery since its properties hinder its manufacture into the dosage form and restrict its regulated delivery from such a dosage form.
It is immediately apparent, in the light of the above presentation, that an urgent need exists for a dosage form endowed with controlled-release delivery for administering valproic acid and its derivatives for antiepileptic valproic therapy. The need exists for this dosage form for delivering antiepileptic valproic acid in a controlled sustained dose in a therapeutic drug range and simultaneously provide extended therapy. It will be appreciated by those versed in the dispensing antiepileptic drug art, that a dosage form that can administer an antiepileptic valproic drug in to provide a controlled-rate dose over time, it would be seen as major advancement in the therapy of the epilepsies.